Infection vs. Contamination

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1 Staphylococcus sp. 90 Min. Identification of S. aureus and Coagulase-Negative Staph from Positive Blood Cultures Infection vs. Contamination

2 In this study we demonstrate that combining a rapid diagnostic test (PNA FISH) with prompt and direct communication of microbiological results is associated with improved outcomes. Ly et al. Therapeutics and Clinical Risk Management June; 4(3): Accuracy You Can Trust PNA FISH Reliability: Sensitive and Specific PNA FISH tests have been validated on all major blood culture systems and compared to identification results obtained via conventional, phenotypic identification methods. Refer to the package insert for complete performance data. S. aureus (KT001) Conventional Identification S. aureus Other Species* Total S. aureus Negative Total Sensitivity: 100% Specificity: 100% PPV: 100% NPV: 100% * Coagulase Negative Staphylococci (142), Other Species (6) S. aureus/cns (KT005) Conventional Identification S. aureus CNS Other Species* Total S. aureus CNS Negative Total Sensitivity S. aureus: 100% Sensitivity CNS: 100% Specificity: 81.8% PPV S. aureus: 100% PPV CNS: 99% NPV: 100% * Micrococcus spp. (4), Other Species (7)

3 For more information visit The Challenge Appropriate Therapy for Patients with Staphylococcal Bloodstream Infections Staphylococci are the most frequent causes of bloodstream infections. Staphylococci are also the most frequent causes of blood culture contamination. True infections with Staphylococcus aureus present considerable clinical challenges and increase mortality rates, prolong hospital stays and add significant extra costs. Blood culture contamination with Coagulase-Negative Staph (CNS) on the other hand leads to unnecessary coverage with broad-spectrum antibiotic therapy, extra length of stay and unnecessary extra costs. The challenge for clinicians is how to ensure early, appropriate therapy for patients with true S. aureus infections while avoiding unnecessary therapy for patients with contaminated blood cultures. GPCC-Positive Blood Cultures: Species Distribution 1 CNS Contamination (60%) 60% of GPCC-Positive Blood Cultures Leads to unnecessary therapy with broadspectrum antibiotics such as vancomycin Results in extra hospital length of stay (LOS) and more than $4,000 in extra bed, pharmacy and laboratory costs 2 CDC Recommendations: Vancomycin should be discouraged for patients with single positive blood culture and other blood cultures that are negative 3 CNS Bacteremia (10%) 10% of GPCC-Positive Blood Culture Associated with indwelling devices and catheters 4 10% 60% 30% S. aureus Bacteremia (30%) 30% of GPCC-Positive Blood Cultures Associated with high mortality rates and requires early and aggressive therapy Up to 30% of patients with septic shock due to S. aureus receive inappropriate therapy 5 50% of patients with MRSA bloodstream infection receive inappropriate empirical antimicrobial therapy 6 Emergence of vancomycin-intermediate S. aureus (VISA) 7 IDSA recommends higher vancomycin loading dose and higher serum concentrations to improve clinical efficacy due to VISA prevalence 7 GPCC= Gram positive cocci in clusters

4 The Dilemma Staphylococci in Positive Blood Cultures: Infection or Contamination? Gram stain: S. aureus or Coagulase-Negative Staph (CNS)? Cannot distinguish S. aureus from CNS in Gram stain. Dilemma: Does the staphylococci in the positive blood culture represent true infection or contamination? When to escalate therapy for S. aureus infection? When to discontinue therapy for CNS contamination? Culture: Identification in 1-3 days. Conventional culture and phenotypic identification can take an additional 1-3 days. Dilemma: Clinicians can t wait an additional 1-3 days to prescribe antimicrobials to cover for true infections. The Solution 90 Minutes Identification and Differentiation of S. aureus and CNS Gram Stain : Identification directly from Positive Blood Cultures S. aureus CNS 90 minutes, molecular identification and differentiation of S. aureus (green) and Coagulase-Negative Staph (red) directly from positive blood cultures. Results 1-3 days earlier than conventional methods. Identify patients with true S. aureus and CNS infections earlier. Ensure early, aggressive and appropriate therapy for patients with true infections. Identify patients with CNS contaminated blood cultures earlier. Avoid broad-spectrum antimicrobials (e.g. vancomycin) for patients with contaminated blood cultures. Reduce antimicrobial use. Reduce extra hospital length of stay (LOS). Reduce unnecessary bed, pharmacy and laboratory costs.

5 Proven Clinical Benefits Use of PNA FISH to rapidly identify staphylococcal species from positive blood cultures has been shown in clinical studies at major medical centers to significantly improve patient outcomes and reduce costs. Reduce Mortality Prospective, randomized, controlled study of 202 patients (101 usual care, 101 notification) with GPCC-positive blood cultures performed at Washington Hospital Center (Washington, D.C.) 8 80% Reduction 48% Early identification and notification of S. aureus and CNS result by PNA FISH 53% Reduction 17% 8% 10% Usual Care Notification Reduced overall mortality rate by 53% Reduced ICU mortality rate by 80% Reduced ICU mortality rate due to S. aureus BSI by 82% Reduced median antibiotic days for CNS by 2.5 days Overall Mortality ICU Mortality Reduce Length of Stay (LOS) and Antimicrobial Use for CNS Contamination Retrospective study of 87 patients (34 control, 54 PNA FISH) with Coagulase-Negative Staph positive blood culture performed at the University of Maryland Medical Center (Baltimore, MD) 9 2 Day Reduction DDD Reduction Early identification of CNS contamination 2 days reduction in length of stay (LOS) 2.6 Discontinued unnecessary vancomycin use Control Group 2.25 defined daily dose (DDD): (4.5 doses) reduction in vancomycin use LOS (Days) DDD vancymycin/pt 7 Sustained reduction in vancomycin use over 4 years Lower Hospital Costs per Patient University of Maryland Medical Center Study 9 $2,704 $9k $6.3k $985 $3.4k $2.4k $316 $1.2k $0.9k $4,005 $13.6k Bed Pharmacy Lab Total $9.6k Control Group Early identification of CNS contamination $2,704 reduction in hospital bed costs due to reduction in length of stay $985 reduction in pharmacy costs $316 reduction in lab costs Total cost-savings of $4,005 per patient Sustained cost-savings over 4 years

6 Bloodstream Infections and Positive Blood Cultures: tests provide rapid identification results for 95-99% of positive blood cultures. Improving Care and Outcomes Rapid identification of bloodstream pathogens with PNA FISH can help physicians improve antimicrobial selection and has been shown to: Reduce mortality rates for S. aureus bacteremia 8 Reduce unnecessary vancomycin use, LOS and costs due to blood culture contamination 9 Improve time to appropriate therapy for E. faecium bacteremia by 1.8 days 10 Reduce mortality rates for E. faecium bacteremia 10 Improve antifungal selection for candidemia 11 Species Distribution in Positive Blood Cultures Gram Stain - Dilemma Species % of Group GPCC (55%) S. aureus 25% Infection vs. Contamination Coagulase-Negative Staph 75% GPCPC (15%) E. faecalis 40% Ampicillin and E. faecium 25% Vancomycin Resistance Streptococcus sp. 35% GNR (20%) E. coli 35% P. aeruginosa vs. non-p. aeruginosa K. pneumoniae 20% P. aeruginosa 15% Other GNRs 30% Yeast (5%) C. albicans 50% Echinocandin vs. Fluconazole C. glabrata 20% C. parapsilosis 15% Other Candida sp. 15% Other (5%) vs. Conventional Dx (90 Min. vs. 1-3 Days) Blood Draw Conventional Dx Day 1 Day 2 Day 3 Day 4 Positive Blood Culture Gram Stain Conventional Species ID Empiric Therapy Broad Spectrum Therapy Targeted Rx Blood Draw Empiric Therapy Positive Blood Culture Gram Stain Species ID: 90 min. Targeted Rx 1. Ann Clin Microbiol Antimicrob May 10;3:7. 2. JAMA Jan 16;265(3): MMWR 44(RR12);1-13 DATE: Sep 22, Poster D-787. ICAAC San Francisco, CA 5. Chest Aug 20. [Epub ahead of print] 6. Infect Control Hosp Epidemiol Nov;30(11): Clin Infect Dis Aug 1;49(3): Ther Clin Risk Manag Jun;4(3): J Antimicrob Chemother Jul;58(1): Antimicrob Agents Chemother Oct;52(10): Della-Latta et al. ECCMID Poster #P1382 US Headquarter 400 Trade Center Woburn, MA (toll free) (fax) EU Headquarter Bygstubben Vedbaek Denmark AdvanDx. All rights reserved. PN1697B

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